Natural Product: NPC603218

Natural Product IDNPC603218
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 DQTMTQZSOJMZSF-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL8087
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

  Chemical Representations

Standard InCHIKey DQTMTQZSOJMZSF-UHFFFAOYSA-N
Standard InCHI InChI=1S/C21H36O2/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-16-19-17-15-18-20(22)21(19)23/h15,17-18,22-23H,2-14,16H2,1H3
SMILES CCCCCCCCCCCCCCCc1cccc(O)c1O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   320.27 Volume:   372.887
?
Van der Waals volume.
Dense:   0.859 LogP:   7.995
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   4.453
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -6.337
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The logarithm of aqueous solubility value.
Rotatable Bonds:   14.0 Rigid Bonds:   6.0
TPSA:   40.46
?
Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   2.0 Rings:   1.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.294 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.003 Fsp3:   0.714
MCE-18:   6.0
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Accepted GSK Rule:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   1
Chelating Alert:   1 PAINS Alert:   1
Colloidal aggregators:   0.804 Fluc inhibitor:   0.245
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.003
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.019
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.95 Promiscuous compounds:   0.17

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.039 MDCK Permeability:   -4.798
Pgp-inhibitor:   0.003 Pgp-substrate:   0.026
PAMPA:   0.0
?
The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).
 Human Intestinal Absorption (HIA):   0.889
20% Bioavailability (F20%):   0.995 30% Bioavailability (F30%):   0.999
50% Bioavailability (F50%):   0.992

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.023 MRP1:   0.941
Plasma Protein Binding (PPB):   98.417% Volume Distribution (VD):   1.023
Fu: 1.339%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.885
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.948
BSEP inhibitor:   0.372

ADMET: Metabolism

CYP1A2-inhibitor:   0.003 CYP1A2-substrate:   0.348
CYP2C19-inhibitor:   0.028 CYP2C19-substrate:   0.038
CYP2C9-inhibitor:   0.998 CYP2C9-substrate:   0.014
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.124
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.999
CYP2B6-substrate:   0.015 CYP2C8-inhibitor:   0.981
HLM stability:   0.258
?
Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):  5.53 Half-life (T1/2):  0.85

ADMET: Toxicity

hERG Blockers:  0.543 hERG Blockers (10um):  0.925
Human Hepatotoxicity (H-HT):  0.457 Drug-induced Liver Injury (DILI):  0.148
AMES Toxicity:  0.116 Rat Oral Acute Toxicity:  0.252
Maximum Recommended Daily Dose:  0.351 Skin Sensitization:  0.996
Carcinogencity:  0.222 Eye Corrosion:  0.99
Eye Irritation:  0.998 Respiratory Toxicity:  0.977
Drug-induced Neurotoxicity:  0.019 Ototoxicity:  0.222
Hematotoxicity:  0.077 Drug-induced Nephrotoxicity:  0.089
Genotoxicity:  0.0 RPMI-8226 Immunitoxicity:  0.038
A549 Cytotoxicity:  0.936 Hek293 Cytotoxicity:  0.384
BCF:   1.081
?
Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].
 IGC50:   5.131
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.23
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.723
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96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

  Species Source

Organism ID Organism Name Taxonomy Level Family SuperKingdom Isolation Part Collection Location Collection Time Reference
NPO55651 Toxicodendron radicans (L.) Kuntze Genus Anacardiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]

Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].



  NP Quantity Composition/Concentration

Organism ID Organism Name Organism Material Preparation Organism Part NP Quantity (Standard) NP Quantity (Minimum) NP Quantity (Maximum) Quantity Unit Reference

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].



 Biological Activity

Molecular-level activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT650 Individual protein Beta-lactamase pse-1 Escherichia coli IC50 n.a. n.a. ug.mL-1 DOI[10.1016/S0960-894X(01)80506-0]
NPT656 Individual protein Beta-lactamase Staphylococcus aureus IC50 = 1800000.0 ug.mL-1 DOI[10.1016/S0960-894X(01)80506-0]
NPT655 Individual protein Beta-lactamase Proteus mirabilis IC50 n.a. n.a. ug.mL-1 DOI[10.1016/S0960-894X(01)80506-0]
NPT651 Individual protein Beta-lactamase OXA-1 Escherichia coli IC50 n.a. n.a. ug.mL-1 DOI[10.1016/S0960-894X(01)80506-0]
NPT654 Individual protein Beta-lactamase Enterobacter cloacae IC50 = 29000.0 ug.mL-1 DOI[10.1016/S0960-894X(01)80506-0]
NPT652 Individual protein Beta-lactamase TEM Escherichia coli IC50 = 1100000.0 ug.mL-1 DOI[10.1016/S0960-894X(01)80506-0]
NPT653 Individual protein Beta-lactamase Pseudomonas aeruginosa (strain ATCC 15692 / PAO1 / 1C / PRS 101 / LMG12228) IC50 = 48000.0 ug.mL-1 DOI[10.1016/S0960-894X(01)80506-0]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT32 Organism Mus musculus Mus musculus Ear thickness = 68.5 uM PMID[1825847]





 Experimental ADME

Experiment Model Experiment Tissue ADME Type ADME Relation ADME Value ADME Unit Reference





 Experimental Toxicity

Quantitative toxicity

Experiment Model Experiment Organism Toxicity Type Toxicity Relation Toxicity Value Toxicity Unit Reference
- Mus musculus LD50 = 3.806881065 mg/kg TOXRIC

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity Carcinogenicity Mutagenicity Cardiotoxicity Respiratory Toxicity Eye Irritation Endocrine Disruption
Hepatotoxicity Carcinogenicity Mutagenicity Cardiotoxicity Respiratory Toxicity Eye Irritation Endocrine Disruption

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]


  Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

●  The left chart: Distribution of similarity level between NPC603218 and all remaining natural products in the NPASS database.
●  The right table: Most similar natural products (Tc>=0.5 or Top200).

Similarity Score Similarity Level Natural Product ID
0.5263 Remote Similarity NPC123273
0.5263 Remote Similarity NPC318325
0.525 Remote Similarity NPC3358
0.525 Remote Similarity NPC306884
0.525 Remote Similarity NPC603092

Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

●  The left chart: Distribution of similarity level between NPC603218 and all drugs/candidates.
●  The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

Similarity Score Similarity Level Drug ID Developmental Stage
0.5385 Remote Similarity NPD846 Phase 4

Bioactivity similarity

  Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.
Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity
B: biological targets similarity
C: networks similarity
D: cell-based bioactivity similarity
E: similarity based on clinical data